Identification of a novel MDM2-p53 interaction inhibitor using virtual screening and docking strategy

Abstract:

In this study we employed a docking approach based on virtual screening to search for inhibitors that can bind to MDM2 and block MDM2-p53 interaction. Candidate compounds were obtained from SPECS library. We processed two rounds of molecular docking. Putative compounds were selected based on binding score ranking and 3D structure inspection. Furthermore, the selected small molecules were validated by cell-based experiments. Treatment of several cancer cells with M12 led to activating p53, and upregulation of p21, leading to cell cycle arrest and apoptosis. To this end, we discovered a novel small molecule named M12 that is structurally different from the known MDM2 antagonists, M12 may be a novel small compound and a potentially useful drug candidate for cancer treatment.